Pinostrobin inhibits proliferation and induces apoptosis in cancer stem-like cells through a reactive oxygen species-dependent mechanism

Abstract

Current treatments and targeted therapies for malignancies are limited due to their severe toxicity and the development of resistance against such treatments, which leads to relapse. Past evidence has indicated that a number of plant-derived dietary agents possess biological activity against highly tumorigenic and resistant cell populations associated with cancer relapse. These subpopulations, termed cancer stem-like cells (CSCs), have been targeted with plant-derived dietary flavonoids. The present study was undertaken to assess the anti-proliferative potential of pinostrobin, a dietary flavonoid, against CSCs. Sphere-forming cells were developed from HeLa cell lines using specific culture conditions. The existence of a CSC population was confirmed by the morphological examination and analysis of surface markers using confocal microscopy and flow cytometry. The effect of pinostrobin on the cell viability of the CSC population, evaluated through MTT reduction assays and the expression levels of surface markers (CD44⁺ and CD24⁺), was studied through various biological assays. HeLa-derived CSCs showed higher CD44⁺ and lower CD24⁺ expression. Pinostrobin inhibited the self-renewal capacity and sphere formation efficiency of CSCs in a dose-dependent manner. Increased ROS production, and decreased mitochondrial membrane potential and CD44⁺ expression indicated that pinostrobin promoted ROS-mediated apoptosis in CSCs. These results thus demonstrate the therapeutic potential and effectiveness of pinostrobin in the chemoprevention and relapse of cancer by targeting the CSC population. Thus, pinostrobin, in combination with currently available chemo and radiation therapies, could possibly be used as a safe strategy to alleviate adverse treatment effects, together with enhancing the efficacy.